Impaired islet turnover in human donor pancreata with aging
Abstract
Objective: The prevalence of type 2 diabetes mellitus escalates with aging although β-cell mass, a primary parameter of β-cell function, is subject to compensatory regulation. So far it is unclear whether the proliferative capacity of pancreatic islets is restricted by senescence. Materials and methods: Human pancreatic tissue from n=20 non-diabetic organ donors with a mean age of 50.2±3.5 years (range 7–66 years) and mean body mass index of 25.7±0.9 kg/m 2 (17.2–33.1 kg/m 2) was morphometrically analyzed to determine β-cell volume, β-cell replication, β-cell apoptosis, islet neogenesis, and pancreatic duodenal homeobox-1 (PDX-1) expression. Results: Relative β-cell volume in human pancreata (mean 2.3±0.2%) remains constant with aging (r=0.26, P=ns). β-cell replication (r=0.71, P=0.0004) decreases age-dependently, while β-cell apoptosis does not change significantly (r=0.42, P=0.08). Concomitantly, PDX-1 expression is downregulated with age in human pancreatic tissue (r=0.65, P=0.002). The rate of islet neogenesis is not affected by aging (r=0.13, P=ns). Conclusions: In non-diabetic humans, aging is linked with impaired islet turnover possibly due to reduced PDX-1 expression. As β-cell replication is considered to be the main mechanism responsible for β-cell regeneration, these changes restrict the flexibility of the aging human pancreas to adapt to changing demands for insulin secretion and increase the risk for the development of diabetes mellitus in older subjects.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Age-related declines of pancreatic islet function and of islet proliferative capacity have been described.
“However, age-related declines of pancreatic islet function4, 14 and of islet proliferative capacity15, 16; have been described.”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Aging Correlates With Decreased β-Cell Proliferative Capacity and Enhanced Sensitivity to Apoptosis
Maedler, K., Schumann, D. M., Schulthess, F., Oberholzer, J., Bosco, D., Berney, T., & Donath, M. Y. (2006) · Diabetes · doi:10.2337/db05-1586 · Cited by 158 · see citing works
Retractedβ-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.1.102 · Cited by 4,011 · see citing works
Self-citationAdult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Dor, Y., Brown, J., Martinez, O. I., & Melton, D. A. (2004) · Nature · doi:10.1038/nature02520 · Cited by 2,219 · see citing works
Projection of Diabetes Burden Through 2050
Boyle, J. P., Honeycutt, A. A., Narayan, K. M. V., Hoerger, T. J., Geiss, L. S., Chen, H., & Thompson, T. J. (2001) · Diabetes Care · doi:10.2337/diacare.24.11.1936 · Cited by 1,004 · see citing works
Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus
Lorenzo, A., Razzaboni, B. L., Weir, G. C., & Yankner, B. A. (1994) · Nature · doi:10.1038/368756a0 · Cited by 819 · see citing works
Meier, J. J., Butler, A. E., Saisho, Y., Monchamp, T., Galasso, R., Bhushan, A., Rizza, R. A., & Butler, P. C. (2008) · Diabetes · doi:10.2337/db07-1369 · Cited by 683 · see citing works
Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited.
Klöppel, G., Löhr, M., Habich, K., Oberholzer, M., & Heitz, P. (1985) · Survey and Synthesis of Pathology Research · doi:10.1159/000156969 · Cited by 645 · see citing works
Recovery from diabetes in mice by β cell regeneration
Nir, T., Melton, D. A., & Dor, Y. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32959 · Cited by 595 · see citing works
Innate immunity in aging: impact on macrophage function
Plowden, J., Renshaw‐Hoelscher, M., Engleman, C., Katz, J. M., & Sambhara, S. R. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00102.x · Cited by 430 · see citing works
Apoptosis Participates in the Remodeling of the Endocrine Pancreas in the Neonatal Rat
Scaglia, L., Cahill, C. J., Finegood, D. T., & Bonner‐Weir, S. (1997) · Endocrinology · doi:10.1210/endo.138.4.5069 · Cited by 418 · see citing works
Cellular composition of the human diabetic pancreas
Rahier, J., Goebbels, R. M., & Henquin, J. C. (1983) · Diabetologia · doi:10.1007/bf00251826 · Cited by 395 · see citing works
New sources of pancreatic β-cells
Bonner‐Weir, S., & Weir, G. C. (2005) · Nature Biotechnology · doi:10.1038/nbt1115 · Cited by 390 · see citing works
DeFronzo, R. A. (1981) · Diabetes Care · doi:10.2337/diacare.4.4.493 · Cited by 389 · see citing works
Insulin Action and Age: European Group for the Study of Insulin Resistance (EGIR)
Ferrannini, E., Vichi, S., Beck-Nielsen, H., Laakso, M., Paolisso, L., & Smith, G. (1996) · Diabetes · doi:10.2337/diab.45.7.947 · Cited by 353 · see citing works
CHEN, M., BERGMAN, R. N., PACINI, G., & PORTE, D. (1985) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-60-1-13 · Cited by 353 · see citing works
Sharma, A., Zangen, D., Reitz, P., Taneja, M., Lissauer, M. E., Miller, C. P., Weir, G. C., Habener, J. F., & Bonner‐Weir, S. (1999) · Diabetes · doi:10.2337/diabetes.48.3.507 · Cited by 331 · see citing works
Chakrabarti, S. K., James, J. C., & Mirmira, R. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111857200 · Cited by 284 · see citing works
Gremlich, S., Bonny, C., Waeber, G., & Thorens, B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.48.30261 · Cited by 276 · see citing works
The replication of β cells in normal physiology, in disease and for therapy
Butler, P. C., Meier, J. J., Butler, A. E., & Bhushan, A. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0647 · Cited by 268 · see citing works
Li, Y., Cao, X., Li, L., Brubaker, P. L., Edlund, H., & Drucker, D. J. (2005) · Diabetes · doi:10.2337/diabetes.54.2.482 · Cited by 247 · see citing works
Relationship Between β-Cell Mass and Fasting Blood Glucose Concentration in Humans
Ritzel, R. A., Butler, A. E., Rizza, R. A., Veldhuis, J. D., & Butler, P. C. (2006) · Diabetes Care · doi:10.2337/diacare.29.03.06.dc05-1538 · Cited by 197 · see citing works
Self-citationSaisho, Y., Butler, A., Meier, J. J., Monchamp, T., Allen-Auerbach, M., Rizza, R., & Butler, P. (2007) · Clinical anatomy (New York, N.Y. Print) · doi:10.1002/ca.20543 · Cited by 175 · see citing works
Marshak, S., Leibowitz, G., Bertuzzi, F., SOCCI, C., Kaiser, Ν., Gross, D. J., Cerasi, E., & Melloul, D. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1230 · Cited by 167 · see citing works
Olson, L. K., Sharma, A., Peshavaria, M., Wright, C. V. E., Towle, H. C., Rodertson, R. P., & Stein, R. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9127 · Cited by 149 · see citing works
Replication Increases β-Cell Vulnerability to Human Islet Amyloid Polypeptide-Induced Apoptosis
Ritzel, R. A., & Butler, P. C. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1701 · Cited by 115 · see citing works
Self-citationPhosphorylation-Dependent Nucleocytoplasmic Shuttling of Pancreatic Duodenal Homeobox-1
Elrick, L. J., & Docherty, K. (2001) · Diabetes · doi:10.2337/diabetes.50.10.2244 · Cited by 111 · see citing works
Age-related skeletal muscle dysfunction: causes and mechanisms.
Degens, H. (2007) · PubMed · Cited by 103 · see citing works
Transcription Factor Occupancy of the Insulin Gene in Vivo
Cissell, M. A., Zhao, L., Sussel, L., Henderson, E., & Stein, R. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m205905200 · Cited by 83 · see citing works
Pancreatic Islets of Obese Hyperglycemic Mice (ob/ob)
Tomita, T., Doull, V., POLLOCK, H. G., & Krizsan, D. (1992) · Pancreas · doi:10.1097/00006676-199205000-00015 · Cited by 75 · see citing works
Røder, M., Schwartz, R. S., Prigeon, R., & Kahn, S. E. (2000) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jcem.85.6.6635 · Cited by 61 · see citing works
Ihm, S., Moon, H. J., Kang, J. G., Park, C., Oh, K. W., Jeong, I., Oh, Y., & Park, S. W. (2007) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2007.01.049 · Cited by 46 · see citing works
Effect of aging on liver regeneration in rats
Biondo-Simões, M. D. L. P., Matias, J. E. F., Montibeller, G. R., Siqueira, L. C. D., Nunes, E. D. S., & Grassi, C. A. (2006) · Acta Cirúrgica Brasileira · doi:10.1590/s0102-86502006000400002 · Cited by 39 · see citing works
PDX-1 expression and proliferation of duct epithelial cells after partial pancreatectomy in rats.
Liu, T., Wang, C., Gou, S., Wu, H., Xiong, J., & Zhou, J. (2007) · PubMed · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kirkman, M. S., Briscoe, V. J., Clark, N., Florez, H., Haas, L. B., Halter, J. B., Huang, E. S., Korytkowski, M. T., Munshi, M. N., Odegard, P. S., et al. (2012) · Diabetes Care · doi:10.2337/dc12-1801 · Cited by 1,274 · see citing works
Beta Cell Dysfunction and Insulin Resistance
Cerf, M. E. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00037 · Cited by 964 · see citing works
Diabetes in Older Adults: A Consensus Report
Sue Kirkman, M., Briscoe, V. J., Clark, N., Florez, H., Haas, L. B., Halter, J. B., Huang, E. S., Korytkowski, M. T., Munshi, M. N., Odegard, P. S., et al. (2012) · Journal of the American Geriatrics Society · doi:10.1111/jgs.12035 · Cited by 548 · see citing works
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 389 · see citing works
Oxidative stress and the ageing endocrine system
Vitale, G., Salvioli, S., & Franceschi, C. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.29 · Cited by 269 · see citing works
Targeting the pancreatic β-cell to treat diabetes
Vetere, A., Choudhary, A., Burns, S. M., & Wagner, B. K. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4231 · Cited by 253 · see citing works
Cnop, M., Hughes, S. J., Igoillo‐Esteve, M., Hoppa, M. B., Sayyed, F., van de Laar, L., Gunter, J. H., de Koning, E. J. P., Walls, G. V., Gray, D. W. G., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1562-x · Cited by 240 · see citing works
β-Cell Growth and Regeneration: Replication Is Only Part of the Story
Bonner‐Weir, S., Li, W., Ouziel-Yahalom, L., Guo, L., Weir, G. C., & Sharma, A. (2010) · Diabetes · doi:10.2337/db10-0084 · Cited by 233 · see citing works
The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations
Lee, P., & Halter, J. B. (2017) · Diabetes Care · doi:10.2337/dc16-1732 · Cited by 211 · see citing works
MicroRNA-7 Regulates the mTOR Pathway and Proliferation in Adult Pancreatic β-Cells
Wang, Y., Liu, J., Liu, C., Naji, A., & Stoffers, D. A. (2012) · Diabetes · doi:10.2337/db12-0451 · Cited by 191 · see citing works
Type 2 Diabetes and the Aging Pancreatic Beta Cell
Gunasekaran, U., & GANNON, M. A. (2011) · Aging · doi:10.18632/aging.100350 · Cited by 183 · see citing works
Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas
Wang, Y. J., Golson, M. L., Schug, J., Traum, D., Liu, C., Vivek, K., Dorrell, C., Naji, A., Powers, A. C., Chang, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.007 · Cited by 157 · see citing works
Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis
Cohrs, C. M., Panzer, J. K., Drotar, D. M., Enos, S. J., Kipke, N., Chen, C., Bozsak, R., Schöniger, E., Ehehalt, F., Distler, M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.033 · Cited by 154 · see citing works
Age-Related Impairment of Pancreatic Beta-Cell Function: Pathophysiological and Cellular Mechanisms
Tata, V. D. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00138 · Cited by 144 · see citing works
Pancreatic Function, Type 2 Diabetes, and Metabolism in Aging
Gong, Z., & Muzumdar, R. H. (2012) · International Journal of Endocrinology · doi:10.1155/2012/320482 · Cited by 130 · see citing works
Pancreatic β-cell identity in diabetes
Remedi, M. S., & Emfinger, C. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12727 · Cited by 128 · see citing works
Murakami, T., Inagaki, N., & Kondoh, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.869414 · Cited by 134 · see citing works
MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview
Diamanti‐Kandarakis, E., Dattilo, M., Μacut, D., Duntas, L. H., Gonos, E. S., Goulis, D. G., Kanaka‐Gantenbein, C., Καπετάνου, Μ., Koukkou, E. G., Lambrinoudaki, I. V., et al. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-1061 · Cited by 103 · see citing works
Longevity of human islet α ‐ and β ‐cells
Cnop, M., Igoillo‐Esteve, M., Hughes, S. J., Walker, J. N., Cnop, I., & Clark, A. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01443.x · Cited by 97 · see citing works
Influence of Donor Age on Islet Isolation and Transplantation Outcome
Niclauß, N., Bosco, D., Morel, P., Demuylder-Mischler, S., Brault, C., Guittard, L., Colin, C., Parnaud, G., Müller, Y. D., Giovannoni, L., et al. (2010) · Transplantation · doi:10.1097/tp.0b013e31820385e6 · Cited by 95 · see citing works
β cell aging and age-related diabetes
Zhu, M., Liu, X., Liu, W., Lu, Y., Cheng, J., & Chen, Y. (2021) · Aging · doi:10.18632/aging.202593 · Cited by 93 · see citing works
The Human Islet: Mini-Organ With Mega-Impact
Walker, J. T., Saunders, D. C., Briššová, M., & Powers, A. C. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab010 · Cited by 80 · see citing works
The pancreatic β-cell in ageing: Implications in age-related diabetes
Tudurí, E., Soriano, S., Almagro, L., Montanya, E., Alonso‐Magdalena, P., Nadal, Á., & Quesada, I. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101674 · Cited by 87 · see citing works
Concise Review: Pancreas Regeneration: Recent Advances and Perspectives
Lysy, P. A., Weir, G. C., & Bonner‐Weir, S. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2011-0025 · Cited by 70 · see citing works
Berney, T., & Johnson, P. (2010) · Transplantation · doi:10.1097/tp.0b013e3181e25a40 · Cited by 70 · see citing works
Towards a Functional Cure for Diabetes Using Stem Cell-Derived Beta Cells: Are We There Yet?
Bourgeois, S., Sawatani, T., Mulders, A. V., Leu, N. D., Heremans, Y., Heimberg, H., Cnop, M., & Staels, W. (2021) · Cells · doi:10.3390/cells10010191 · Cited by 70 · see citing works
Islet Neogenesis: A Possible Pathway for Beta-Cell Replenishment
Bonner‐Weir, S., Guo, L., Li, W., Ouziel-Yahalom, L., Weir, G. C., & Sharma, A. (2012) · The Review of Diabetic Studies · doi:10.1900/rds.2012.9.407 · Cited by 65 · see citing works
Expression profiling of cell cycle genes in human pancreatic islets with and without type 2 diabetes
Taneera, J., Fadista, J., Ahlqvist, E., Zhang, M., Wierup, N., Renström, E., & Groop, L. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.05.003 · Cited by 64 · see citing works
Stem cell approaches for diabetes: towards beta cell replacement
Weir, G. C., Cavelti‐Weder, C., & Bonner‐Weir, S. (2011) · Genome Medicine · doi:10.1186/gm277 · Cited by 59 · see citing works
In Vitro Proliferation of Adult Human Beta-Cells
Rütti, S., Sauter, N. S., Bouzakri, K., Prazak, R., Halban, P. A., & Donath, M. Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035801 · Cited by 54 · see citing works
Age‐associated changes of islet endocrine cells and the effects of body mass index in J apanese
Mizukami, H., Takahashi, K., Inaba, W., Osonoi, S., Kamata, K., Tsuboi, K., & Yagihashi, S. (2013) · Journal of Diabetes Investigation · doi:10.1111/jdi.12118 · Cited by 55 · see citing works
β-Cell Telomere Attrition in Diabetes: Inverse Correlation Between HbA1c and Telomere Length
Tamura, Y., Izumiyama‐Shimomura, N., Kimbara, Y., Nakamura, K., Ishikawa, N., Aida, J., Chiba, Y., Mori, S., Arai, T., Aizawa, T., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1222 · Cited by 53 · see citing works
Making β Cells from Adult Cells Within the Pancreas
Lysy, P. A., Weir, G. C., & Bonner‐Weir, S. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0400-1 · Cited by 50 · see citing works
Type 2 Diabetes in the Elderly: Challenges in a Unique Patient Population
Bradley, D. P. (2016) · Journal of Geriatric Medicine and Gerontology · doi:10.23937/2469-5858/1510014 · Cited by 55 · see citing works
Comparison of exendin-4 on beta-cell replication in mouse and human islet grafts
Tian, L., Gao, J., Weng, G., Yi, H., Tian, B., O’Brien, T. D., & Guo, Z. (2011) · Transplant International · doi:10.1111/j.1432-2277.2011.01275.x · Cited by 47 · see citing works
Quantitative analysis of intra- and inter-individual variability of human beta-cell mass
Olehnik, S. K., Fowler, J. L., Avramovich, G., & Hara, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-16300-w · Cited by 47 · see citing works
Topologically Heterogeneous Beta Cell Adaptation in Response to High-Fat Diet in Mice
Ellenbroek, J. H., Töns, H. A. M., de Graaf, N., Loomans, C. J. M., Engelse, M. A., Vrolijk, H., Voshol, P. J., Rabelink, T. J., Carlotti, F., & de Koning, E. J. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056922 · Cited by 46 · see citing works
The regulation of pre- and post-maturational plasticity of mammalian islet cell mass
Mezza, T., & Kulkarni, R. (2014) · Diabetologia · doi:10.1007/s00125-014-3251-7 · Cited by 44 · see citing works
Adaptive changes of human islets to an obesogenic environment in the mouse
Gargani, S., Thévenet, J., Yuan, J.-E., Lefebvre, B., Delalleau, N., Gmyr, V., Hubert, T., Duhamel, A., Pattou, F., & Kerr-Conte, J. (2012) · Diabetologia · doi:10.1007/s00125-012-2775-y · Cited by 43 · see citing works
Kurauti, M. A., Soares, G. M., Marmentini, C., Bronczek, G. A., Branco, R. C. S., & Boschero, A. C. (2021) · Vitamins and hormones · doi:10.1016/bs.vh.2020.12.010 · Cited by 44 · see citing works
The entrancing role of dietary polyphenols against the most frequent aging‐associated diseases
Shah, M. A., Faheem, H. I., Hamid, A., Yousaf, R., Haris, M., Saleem, U., Shah, G. M., Alhasani, R. H., Althobaiti, N. A., Alsharif, I., et al. (2023) · Medicinal Research Reviews · doi:10.1002/med.21985 · Cited by 42 · see citing works
He, W., Yuan, T., Choezom, D., Hunkler, H. J., Annamalai, K., Lupše, B., & Maedler, K. (2018) · Scientific Reports · doi:10.1038/s41598-018-20909-w · Cited by 40 · see citing works
Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor
Ansarullah, M., Lu, Y., Holstein, M., Brittany, D., Rabinovitch, A., & Guo, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053345 · Cited by 38 · see citing works
Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system
Kehm, R., König, J., Nowotny, K., Jung, T., Deubel, S., Gohlke, S., Schulz, T. J., & Höhn, A. (2017) · Redox Biology · doi:10.1016/j.redox.2017.12.015 · Cited by 38 · see citing works
Nakagawa, K., Takasawa, S., Nata, K., Yamauchi, A., Itaya‐Hironaka, A., Ota, H., Yoshimoto, K., Sakuramoto‐Tsuchida, S., Miyaoka, T., Takeda, M., et al. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.08.004 · Cited by 33 · see citing works
Márquez-Aguirre, A. L., Canales-Aguirre, A. A., Padilla‐Camberos, E., Esquivel‐Solís, H., & Diaz-Martinez, N. E. (2015) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20154363 · Cited by 32 · see citing works
Golson, M. L., Dunn, J. C., Maulis, M. F., Dadi, P. K., Osipovich, A. B., Magnuson, M. A., Jacobson, D. A., & GANNON, M. A. (2015) · Diabetes · doi:10.2337/db15-0465 · Cited by 31 · see citing works
Ardestani, A. D., Sauter, N. S., Paroni, F., Dharmadhikari, G., Cho, J., Lupi, R., Marchetti, P., Oberholzer, J., Kerr-Conte, J., & Maedler, K. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.210526 · Cited by 29 · see citing works
RetractedHeterogeneity and Dynamics of Vasculature in the Endocrine System During Aging and Disease
Stücker, S., Angelis, J. E. D., & Kusumbe, A. P. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.624928 · Cited by 32 · see citing works
Gaetano, A. D., & Hardy, T. A. (2019) · PLoS ONE · doi:10.1371/journal.pone.0222833 · Cited by 29 · see citing works
Guardado‐Mendoza, R., Jiménez-Ceja, L. M., Majluf‐Cruz, A., Kamath, S., Fiorentino, T. V., Casiraghi, F., Velazquez, A. O. C., DeFronzo, R. A., Dick, E. J., Davalli, A. M., et al. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.205 · Cited by 27 · see citing works
Caballero, F., Siniakowicz, K., Hollister‐Lock, J., Duran, L., Katsuta, H., Yamada, T., Lei, J., Deng, S., Westermark, G. T., Markmann, J. F., et al. (2013) · Cell Transplantation · doi:10.3727/096368912x659916 · Cited by 27 · see citing works
Sionov, R. V., Finesilver, G., Sapozhnikov, L., Soroker, A., Zlotkin‐Rivkin, E., Saad, Y., Kahana, M., Bodaker, M., Alpert, E., & Mitrani, E. (2015) · Tissue Engineering Part A · doi:10.1089/ten.tea.2014.0711 · Cited by 22 · see citing works
Tatsuoka, H., Sakamoto, S., Yabe, D., Kabai, R., Kato, U., Okumura, T., Botagarova, A., Tokumoto, S., Usui, R., Ogura, M., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101774 · Cited by 22 · see citing works
Köhler, C. U., Kreuter, A., Rozynkowski, M., Rahmel, T., Uhl, W. H., Tannapfel, A., Schmidt, W. E., & Meier, J. J. (2010) · Regulatory Peptides · doi:10.1016/j.regpep.2009.12.021 · Cited by 21 · see citing works
Liu, J., Yy, W., Huang, X.-M., Yang, M. L., Bb, Z., WANG, F., Zha, Y., Sheng, L., Zp, C., & Gu, Y. (2014) · PubMed · Cited by 20 · see citing works
Chen, X., Zhang, X., Chen, F., Larson, C. S., Wang, L.-J., & Kaufman, D. B. (2009) · Transplantation · doi:10.1097/tp.0b013e3181b0d2ee · Cited by 20 · see citing works
Intrapancreatic adipocytes and beta cell dedifferentiation in human type 2 diabetes
Zhang, N., Sun, Q., Zhang, J., Zhang, R., Liu, S., Zhao, X., Ma, J., & Li, X. (2025) · Diabetologia · doi:10.1007/s00125-025-06392-9 · Cited by 18 · see citing works
An update on pancreatic regeneration mechanisms: Searching for paths to a cure for type 2 diabetes
Soldovieri, L., Giuseppe, G. D., Ciccarelli, G., Quero, G., Cinti, F., Brunetti, M., Nista, E. C., Gasbarrini, A., Alfieri, S., Pontecorvi, A., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101754 · Cited by 19 · see citing works
The long noncoding RNA TUNAR modulates Wnt signaling and regulates human β-cell proliferation
Zhou, A., Mondal, T., Tabish, A. M., Abadpour, S., Ericson, E., Smith, D. M., Knöll, R., Scholz, H., Kanduri, C., Tyrberg, B., et al. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00335.2020 · Cited by 17 · see citing works
Pancreatic α‐cell mass in obesity
Ellenbroek, J. H., Töns, H. A. M., Hanegraaf, M. A. J., Rabelink, T. J., Engelse, M. A., Carlotti, F., & de Koning, E. J. P. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12997 · Cited by 17 · see citing works
Hanefeld, M., Berria, R., Lin, J., Aronson, R., Darmon, P., Evans, M., & Gaal, L. V. (2014) · Advances in Therapy · doi:10.1007/s12325-014-0146-4 · Cited by 16 · see citing works
Tresguerres, J. A. F., Cuesta‐Sancho, S., Kireev, R. A., Garcı́a, C., Acuña-Castroviejo, D., & Vara, E. (2013) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2013-0041 · Cited by 16 · see citing works
Huang, L., Jiang, X., Gong, L., & Xing, D. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25133 · Cited by 16 · see citing works
β-Cell Generation: Can Rodent Studies Be Translated to Humans?
Carlotti, F., Zaldumbide, A., Ellenbroek, J. H., Spijker, H. S., Hoeben, R. C., & de Koning, E. J. P. (2011) · Journal of Transplantation · doi:10.1155/2011/892453 · Cited by 15 · see citing works
Ansarullah, M., Free, C., Christopherson, J., Chen, Q., Gao, J., Liu, C., Naji, A., Rabinovitch, A., & Guo, Z. (2016) · Journal of Diabetes Research · doi:10.1155/2016/1620821 · Cited by 15 · see citing works
TRPM7 kinase is required for insulin production and compensatory islet responses during obesity
Khajavi, N., Beck, A., Riçku, K., Beyerle, P., Jacob, K., Syamsul, S. F., Belkacemi, A., Reinach, P. S., Schreier, P. C. F., Salah, H., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.163397 · Cited by 14 · see citing works
Telomere attrition in beta and alpha cells with age
Tamura, Y., Izumiyama‐Shimomura, N., Kimbara, Y., Nakamura, K., Ishikawa, N., Aida, J., Chiba, Y., Matsuda, Y., Mori, S., Arai, T., et al. (2016) · AGE · doi:10.1007/s11357-016-9923-0 · Cited by 14 · see citing works
Decreased β‐cell insulin secretory function in aged rats due to impaired Ca2+ handling
Ribeiro, R. A., Batista, T. M., Coelho, F. M., Boschero, A. C., Lopes, G. S., & Carneiro, E. M. (2012) · Experimental Physiology · doi:10.1113/expphysiol.2012.064790 · Cited by 12 · see citing works
Modelling age-related metabolic disorders in the mouse
Goldsworthy, M. E., & Potter, P. K. (2014) · Mammalian Genome · doi:10.1007/s00335-014-9539-6 · Cited by 12 · see citing works
The older patient with diabetes: a practical approach
Ben‐Yehuda, A., Zinger, A., & Durso, S. C. (2013) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2485 · Cited by 11 · see citing works
Adult tissue sources for new β cells
Nichols, R. J., New, C., & Annes, J. P. (2013) · Translational research · doi:10.1016/j.trsl.2013.11.012 · Cited by 11 · see citing works
Impaired glucose metabolism and type 2 diabetes in apparently healthy senior citizens
Escobar, P. M., Moser, M., Risch, L., Risch, M., Nydegger, U., & Stanga, Z. G. (2015) · Swiss Medical Weekly · doi:10.4414/smw.2015.14209 · Cited by 11 · see citing works
Differential expression of cell-cycle regulators in human beta-cells derived from insulinoma tissue
Ueberberg, S., Tannapfel, A., Schenker, P., Viebahn, R., Uhl, W. H., Schneider, S., & Meier, J. J. (2016) · Metabolism · doi:10.1016/j.metabol.2016.02.007 · Cited by 10 · see citing works
Mohammed, H., & Salloom, D. F. (2020) · Meta Gene · doi:10.1016/j.mgene.2020.100845 · Cited by 9 · see citing works
Extra-islet cells expressing insulin or glucagon in the pancreas of young organ donors
Granlund, L., Korsgren, O., Skog, O., & Lundberg, M. (2024) · Acta Diabetologica · doi:10.1007/s00592-024-02295-0 · Cited by 7 · see citing works
Hahm, J., Kumar, D., Andrade, J. A. F., Arany, E. J., & Hill, D. J. (2025) · Cells · doi:10.3390/cells14010034 · Cited by 6 · see citing works
Brown, J. E. P. (2012) · The British Journal of Diabetes · doi:10.1177/1474651412446713 · Cited by 6 · see citing works
Non-ICU Hospital Care of Diabetes Mellitus in the Elderly Population
Gilden, J. L., & Gupta, A. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0596-3 · Cited by 5 · see citing works
Glucose Metabolism, Insulin, and Aging
Boemi, M., Furlan, G., & Luconi, M. P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801816-3.00029-7 · Cited by 4 · see citing works
Gallo, S., Raji, A., Calle, R. A., Pong, A., & Meyer, C. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14149 · Cited by 5 · see citing works
Azad, A., Altunbaş, H., & Manguoğlu, A. E. (2024) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2024.2347263 · Cited by 5 · see citing works
Kasperová, B. J., Cinkajzlová, A., Horváth, L., Svoboda, P., Haluzı́k, M., & Hubáčková, S. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1622107 · Cited by 4 · see citing works
Pancreatic β‐cell turnover in health and disease
Alcibahy, Y., Darwish, R., Butler, A. E., & Moin, A. S. M. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.70191 · Cited by 6 · see citing works
Chen, H.-Y., Chen, D.-T., Chiang, Y.-Y., Lin, S., & Lee, C. (2022) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2022.02.045 · Cited by 4 · see citing works
Chia, C. W., & Ferrucci, L. (2014) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2305-5839.2014.10.05 · Cited by 4 · see citing works
Degradation meets development: Implications in β‐cell development and diabetes
Ashok, A., Kalthur, G., & Kumar, A. (2024) · Cell Biology International · doi:10.1002/cbin.12155 · Cited by 2 · see citing works
Markers of insulin resistance and their performance in adult Nigerians with metabolic syndrome
Udenze, I. C., Taiwo, I., Minari, J. B., & Amadi, C. E. (2019) · International Journal of Noncommunicable Diseases · doi:10.4103/jncd.jncd_53_18 · Cited by 3 · see citing works
Human beta cell proliferation by glucose—a complex scenario
Tiedge, M. (2010) · Diabetologia · doi:10.1007/s00125-010-2015-2 · Cited by 2 · see citing works
Pancreas Development and Regeneration
Riley, K. G., & GANNON, M. A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405945-0.00031-4 · Cited by 2 · see citing works
Mandal, Š., Čaušević, A., Malenica, M., Hadzidedic, S., Prnjavorac, B., & Semiz, S. (2012) · Journal of Health Sciences · doi:10.17532/jhsci.2012.37 · Cited by 2 · see citing works
Nutrition Issues and Recommendations in the Management of Diabetes and Prediabetes in Older Adults
Stetson, B. A., McDonough, S., & Mokshagundam, S. P. (2015) · Springer eBooks · doi:10.1007/978-3-319-22431-2_21 · Cited by 2 · see citing works
Hudson, M., & Palermo, N. E. (2017) · Springer eBooks · doi:10.1007/978-3-319-20317-1_14-1 · Cited by 2 · see citing works
Pancreatic β-Cell Senescence: Mechanisms and Association with Diabetes
Ahmed, S. M., Elshenawy, S. E., Sedky, S., Elmehrath, A. O., & El‐Badri, N. (2021) · European Medical Journal · doi:10.33590/emj/20-00128 · Cited by 4 · see citing works
The effect of chronic hyperglycemia on aging: implications in cognitive impairment
Sarkar, A., Saha, S., & Bhattacharya, D. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33355-2.00027-x · Cited by 1 · see citing works
Proshchina, A. E., Krivova, Y. S., Barabanov, V. M., & Savelyev, S. V. (2013) · Diabetes Mellitus · doi:10.14341/dm2013438-43 · Cited by 1 · see citing works
Models of Regeneration of Beta Cells in Vivo
Ilie, I. R. P., & Ilie, R. (2013) · Cited by 1 · see citing works
Type 2 Diabetes Mellitus Management in Older Adults with Dementia
Sohail, M., James, K., & Munshi, M. N. (2020) · Springer eBooks · doi:10.1007/978-3-030-46398-4_6 · Cited by 1 · see citing works
Nikhra, V. (2018) · Open Access Journal of Gerontology & Geriatric Medicine · doi:10.19080/oajggm.2018.03.555608 · Cited by 1 · see citing works
Insulin resistance and cardiovascular risk in older adult Nigerians with type 2 diabetes
Udenze, I. C., Taiwo, I., Minari, J. B., & Adeyemo, W. (2019) · International Journal of Noncommunicable Diseases · doi:10.4103/jncd.jncd_43_18 · Cited by 1 · see citing works
- Authors
- Reers, C., Erbel, S., Esposito, I., Schmied, B., Büchler, M. W., Nawroth, P. P., & Ritzel, R. A.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Ritzel, Robert A
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-02
- Volume
- 160
- Issue
- 2
- Pages
- 185-191
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2164058944
- Cited by
- 113
- References
- 33
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 9 · 2013: 16 · 2012: 12
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- aging, beta-cell proliferation, beta-cell apoptosis, islet neogenesis, beta-cell mass, beta cell regeneration, type 2 diabetes risk, human pancreas, organ donors
- MeSH terms
- Adolescent, Adult, Aged, Aging, Cell Division, Child, Diabetes Mellitus, Type 2, Female, Glucagon, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Risk Factors, Tissue Donors, Trans-Activators, Prevalence, Cellular Senescence, Homeodomain Proteins, Insulin-Secreting Cells, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
